National end-stage renal disease (ESRD) registries have revealed that the progression of many renal diseases is more aggressive in men than it is in age-matched pre-menopausal women. The progression o renal disease as well as the risk for cardiovascular disease, bone loss and cognitive function is also much less in post-menopausal women on estrogen replacement therapy (ERT) compared to those without ERT. Thus, hormonal responses within the kidney may be involved in the risk factors associated with ESRD. There is accumulating evidence that estrogen has a regulatory influence on the renin angiotensin system. We propose to investigate the interaction of estrogen with the renin angiotensin system in the 5/6 nephrectomy renal ablation animal model of ESRD. Our first aim is to determine the effects of 17beta-estradiol (E2) on indicators of progressive renal injury in 5/6 nephrectomized rats. We propose to determine the dose and time dependency of E2 on proteinuria, blood pressure, blood urine nitrogen, serum and urine creatinine, and glomerulosclerosis in 5/6 nephrectomized ovariectomized (OVX) female rats and compare these data to aged matched 5/6 nephrectomized males and to sham operated animals. Our second aim is to determine the effects of E2 on renal hemodynamics and ATE receptor expression in 5/6 nephrectomized rats. We will determine the effects of E2 on Ang II- induced changes in renal hemodynamics. We will correlate these findings with the effects of E2 on glomerular angiotensin ATE receptor (R) expression. We will also examine this correlation during angiotensin converting enzyme (ACE) inhibition during Ang II infusion and AT1 receptor blockade. We hypothesize that estrogen will protect renal function as evidenced by an observed attenuation in determinants of progressive renal injury and in preservation of renal hemodynamics. We alsp hypothesize that the ability of estrogen to reduce AT, receptor expression is a major contributing factor in the renal protective effects of estrogen in this animal model. These studies may provide further insight into the mechanisms underlying the well-documented sexual dimorphism observed in the progression of renal pathology and in the increased incidence of EDRD with ovarian senescence.